Our broad objective is to extend and integrate electrochemical (EC) and MS technologies to facilitate a range of metabolomics studies. Our hypothesis is that hyphenated EC-MS will allow for greater elucidation of the metabolome is supported by our preliminary studies, which show that parallel EC-Array and MS substantially extends the scope, qualitative and quantitative capabilities of LC analysis. Additionally, serial EC can assist and control MS ionization and mimic biological redox reactions. Scaling of EC from synthetic to high through put and nanoscale formats and variants of electrode and electronic control allow optimization for specific applications. The specific aims are to: 1. Integrate existing EC and MS technologies for modular use in serial and parallel configurations adaptable to several LC-MS systems. This hyphenated approach for metabolomics will be evaluated with well-characterized multivariate methods to serve as a performance benchmark. 2. Develop innovative EC sensors and reactors, software and detection modalities to substantially extend the range, throughput, quantitative, and qualitative capabilities of both EC and MS as compared to the benchmark. 3. Characterize the developed EC and MS technologies and implement novel strategies for structural elucidation of metabolites and develop a shared knowledge base of qualitative information for use by our collaborators. 4. Characterize technology relevance to multivariate analysis, biological resolution and biomarker discovery using models of xenobiotic toxicity in rats and the widely used biological model C. Elegans. 5. Transfer technology to laboratories with active metabolomics programs to help establish specifications for formal development. 6. Implement production of the technology for wide dissemination to the metabolomics research community.